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We present a novel extension of the path tracing algorithm that is capable of treating highly scattering participating media in the presence of fluorescent structures. The extension is based on the formulation of the full radiative transfer equation when solved on a per-wavelength-basis, resulting in accurate model and unbiased algorithm for rendering highly scattering fluorescent participating media. The model accounts for the intrinsic properties of fluorescent dyes including their absorption and emission spectra, molar absorptivity and quantum yield and also their concentration. Our algorithm is applied to render highly scattering isotropic fluorescent solutions under different illumination conditions. The spectral performance of the model is validated against emission spectra of different fluorescent dyes that are of significance in spectroscopy., Comment: 18 pages, 7 figures, conference

A method is presented for the reduction of morphologically detailed microcircuit models to a point-neuron representation without human intervention. The simplification occurs in a modular workflow, in the neighborhood of a user specified network activity state for the reference model, the "operating point". First, synapses are moved to the soma, correcting for dendritic filtering by low-pass filtering the delivered synaptic current. Filter parameters are computed numerically and independently for inhibitory and excitatory input using a Green's function approach. Next, point-neuron models for each neuron in the microcircuit are fit to their respective morphologically detailed counterparts. Here, generalized integrate-and-fire point neuron models are used, leveraging a recently published fitting toolbox. The fits are constrained by currents and voltages computed in the morphologically detailed partner neurons with soma corrected synapses at three depolarizations about the user specified operating point. The result is a simplified circuit which is well constrained by the reference circuit, and can be continuously updated as the latter iteratively integrates new data. The modularity of the approach makes it applicable also for other point-neuron and synapse models. The approach is demonstrated on a recently reported reconstruction of a neocortical microcircuit around an in vivo-like working point. The resulting simplified network model is benchmarked to the reference morphologically detailed microcircuit model for a range of simulated network protocols. The simplified network is found to be slightly more sub-critical than the reference, with otherwise good agreement for both quantitative and qualitative validations., Comment: Changes since version 1: filter fitting approach replaced by a new method to directly extract the filters using a Green's functions approach. Methods Section 2.1, Results Section 3.1 and Figures 1, 2, 4, 5 have been updated to reflect these changes. Discussion has been updated to incorporate the new findings

Nervous systems are characterized by neurons displaying a diversity of morphological shapes. Traditionally, different shapes have been qualitatively described based on visual inspection and quantitatively described based on morphometric parameters. Neither process provides a solid foundation for categorizing the various morphologies, a problem that is important in many fields. We propose a stable topological measure as a standardized descriptor for any tree-like morphology, which encodes its skeletal branching anatomy. More specifically it is a barcode of the branching tree as determined by a spherical filtration centered at the root or neuronal soma. This Topological Morphology Descriptor (TMD) allows for the discrimination of groups of random and neuronal trees at linear computational cost., Comment: 10 pages, 5 figures, conference or other essential info

At many scales in neuroscience, appropriate mathematical models take the form of complex dynamical systems. Parametrising such models to conform to the multitude of available experimental constraints is a global nonlinear optimisation problem with a complex fitness landscape, requiring numerical techniques to find suitable approximate solutions. Stochastic optimisation approaches, such as evolutionary algorithms, have been shown to be effective, but often the setting up of such optimisations and the choice of a specific search algorithm and its parameters is non-trivial, requiring domain-specific expertise. Here we describe BluePyOpt, a Python package targeted at the broad neuroscience community to simplify this task. BluePyOpt is an extensible framework for data-driven model parameter optimisation that wraps and standardises several existing open-source tools. It simplifies the task of creating and sharing these optimisations, and the associated techniques and knowledge. This is achieved by abstracting the optimisation and evaluation tasks into various reusable and flexible discrete elements according to established best-practices. Further, BluePyOpt provides methods for setting up both small- and large-scale optimisations on a variety of platforms, ranging from laptops to Linux clusters and cloud-based compute infrastructures. The versatility of the BluePyOpt framework is demonstrated by working through three representative neuroscience specific use cases.

A recent publication provides the network graph for a neocortical microcircuit comprising 8 million connections between 31,000 neurons (H. Markram, et al., Reconstruction and simulation of neocortical microcircuitry, Cell, 163 (2015) no. 2, 456-492). Since traditional graph-theoretical methods may not be sufficient to understand the immense complexity of such a biological network, we explored whether methods from algebraic topology could provide a new perspective on its structural and functional organization. Structural topological analysis revealed that directed graphs representing connectivity among neurons in the microcircuit deviated significantly from different varieties of randomized graph. In particular, the directed graphs contained in the order of $10^7$ simplices {\DH} groups of neurons with all-to-all directed connectivity. Some of these simplices contained up to 8 neurons, making them the most extreme neuronal clustering motif ever reported. Functional topological analysis of simulated neuronal activity in the microcircuit revealed novel spatio-temporal metrics that provide an effective classification of functional responses to qualitatively different stimuli. This study represents the first algebraic topological analysis of structural connectomics and connectomics-based spatio-temporal activity in a biologically realistic neural microcircuit. The methods used in the study show promise for more general applications in network science.

Extensive mapping of neuronal connections in the central nervous system requires high-throughput um-scale imaging of large volumes. In recent years, different approaches have been developed to overcome the limitations due to tissue light scattering. These methods are generally developed to improve the performance of a specific imaging modality, thus limiting comprehensive neuroanatomical exploration by multimodal optical techniques. Here, we introduce a versatile brain clearing agent (2,2'-thiodiethanol; TDE) suitable for various applications and imaging techniques. TDE is cost-efficient, water-soluble and low-viscous and, more importantly, it preserves fluorescence, is compatible with immunostaining and does not cause deformations at sub-cellular level. We demonstrate the effectiveness of this method in different applications: in fixed samples by imaging a whole mouse hippocampus with serial two-photon tomography; in combination with CLARITY by reconstructing an entire mouse brain with light sheet microscopy and in translational research by imaging immunostained human dysplastic brain tissue., Comment: in Scientific Reports 2015

Today's scientists are quickly moving from in vitro to in silico experimentation: they no longer analyze natural phenomena in a petri dish, but instead they build models and simulate them. Managing and analyzing the massive amounts of data involved in simulations is a major task. Yet, they lack the tools to efficiently work with data of this size. One problem many scientists share is the analysis of the massive spatial models they build. For several types of analysis they need to interactively follow the structures in the spatial model, e.g., the arterial tree, neuron fibers, etc., and issue range queries along the way. Each query takes long to execute, and the total time for executing a sequence of queries significantly delays data analysis. Prefetching the spatial data reduces the response time considerably, but known approaches do not prefetch with high accuracy. We develop SCOUT, a structure-aware method for prefetching data along interactive spatial query sequences. SCOUT uses an approximate graph model of the structures involved in past queries and attempts to identify what particular structure the user follows. Our experiments with neuroscience data show that SCOUT prefetches with an accuracy from 71% to 92%, which translates to a speedup of 4x-15x. SCOUT also improves the prefetching accuracy on datasets from other scientific domains, such as medicine and biology., Comment: VLDB2012